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Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

The TCL1 oncoprotein inhibits activation-induced cell death by impairing PKCtheta and ERK pathways

Gilles Despouy1, Marjorie Joiner, Emilie Le Toriellec

  • 1Institut Curie, Centre de Recherche, Paris, France.

Blood
|September 12, 2007
PubMed

Insights

The TCL1 oncogene inhibits T-cell activation-induced cell death (AICD) by blocking PKCtheta and ERK pathways. This finding is relevant for understanding T-cell prolymphocytic leukemia (T-PLL) pathogenesis.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • TCL1/MTCP1 oncogenes are implicated in T-cell prolymphocytic leukemia (T-PLL).
  • TCL1 proteins interact with AKT, modulating its signaling pathway, but their role in leukemogenesis is not fully understood.

Purpose of the Study:

  • To investigate the biological functions of TCL1 in T-cell lineage.
  • To elucidate the mechanism by which TCL1 influences T-cell activation and survival.

Main Methods:

  • Utilized various T-cell lines (Jurkat, SUP-T11) and primary malignant and normal lymphocytes.
  • Assessed effects of TCL1 expression on activation-induced cell death (AICD).
  • Analyzed inhibition of PKCtheta and ERK pathways using Western blotting and RNA interference.

Main Results:

  • TCL1 expression abrogated AICD in Jurkat cells and inhibited PKCtheta and ERK pathways.
  • TCL1-driven leukemia cells (SUP-T11) showed impaired PKCtheta and ERK phosphorylation, restored by TCL1 inhibition.
  • Similar pathway defects were observed in primary T-PLL cells and TCL1-transduced normal T lymphocytes.

Conclusions:

  • TCL1 inhibits AICD in T cells by blocking PKCtheta and ERK activation upon cellular stimulation.
  • These findings clarify TCL1's role in T-cell leukemogenesis and suggest potential therapeutic targets.

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